INTRODUCTION: For centuries, METHODS: Here, we investigated the effects of unprocessed Cistanche polysaccharides and wine-processed Cistanche polysaccharides on the metabolism of acteoside RESULTS: The results showed that the Cistanche polysaccharides used in this experiment, including unprocessed Cistanche polysaccharides and wine-processed Cistanche polysaccharides, could regulate the diversity of gut microbiota and increase the number of beneficial bacteria, especially wine-processed Cistanche polysaccharides were able to promote the growth of DISCUSSION: By exploring the synergistic effects of large molecules Cistanche polysaccharides and small molecule acteoside, this paper provides a new explanation for the scientific use of plant-derived polysaccharides to improve the bioavailability of oral drugs.